RESUMEN
Since the awareness of adverse effects associated with pharmaceutical excipients in drug formulations, these excipients are no longer considered inert substances. Numerous countries have recognized the potential risks that they pose to patients and have implemented diverse regulations to evaluate their safety, compatibility, toxicity, and quality. Regulatory authorities have proactively implemented measures to evaluate excipients and have formulated comprehensive guidelines that manufacturers are obligated to follow. This review primarily highlights the different provisions governing the utilization of excipients in drug formulation by regulatory authorities worldwide. Nonetheless, it is worth noting that there are still many countries that do not perceive excipients as posing a potential threat.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Excipientes , Humanos , Excipientes/efectos adversosRESUMEN
Methotrexate (MTX), a biopharmaceutical classification system-IV anticancer drug, exhibits low therapeutic efficacy. Moreover, its clinical applications were restricted due to its multidrug resistance (MDR) in cancer and its toxic effects. The present investigation was to fabricate 1, 2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium (DMPG-Na), (3ß)-cholest-5-en-3-ol (cholesterol) and calcium-based nanocochleates (NCs) as a potential oral delivery carrier for MTX to enhance its therapeutic efficacy with low toxicity. MTX-loaded NCs (MTX-NCs) was developed by the addition of calcium ion into preformed nanoliposomes (MTX-NLs) comprising MTX, DMPG-Na, with cholesterol and evaluated by in-vitro and in-vivo methods in comparison with MTX-NLs and pure MTX. Stable tubular rod structure of MTX-NCs possessing particle size, encapsulation efficiency and zeta potential of 374.1 ± 2.2 nm, 78.63 ± 2.12% and -71.2 mV, respectively were obtained from homogenous unilamellar, discrete and spherical structured MTX-NLs with a diameter and zeta potential of 363.3 ± 3.7 nm and -74.6 mV respectively. A thermal study revealed an amorphous state of MTX in MTX-NCs. Pharmacokinetics study in rats, MTX-NLs and MTX-NCs were showed controlled release with 5 and 6 fold improvements in oral bioavailability. Moreover, MTX-NCs showed low tissue distribution. These results collectively suggest that the developed system could be used to improve the therapeutic efficacy of MTX.
Asunto(s)
Calcio , Metotrexato , Ratas , Animales , Metotrexato/farmacología , Metotrexato/química , Liposomas , Fosfatidilgliceroles/química , Tamaño de la Partícula , Colesterol/química , Excipientes , Portadores de Fármacos/químicaRESUMEN
BACKGROUND: Current therapy for pulmonary arterial hypertension (PAH) is unable to prevent progression of disease due to continuous infusions and multiple oral administrations. This resulted in the need of novel treatment which would target directly structural vascular changes that weaken blood flow through pulmonary circulation. OBJECTIVE: The objective of present study was to develop spray dried (SD) formulation for dry powder inhaler (DPI) with enhanced aerosol performance and lung deposition by using novel bioactive, andrographolide (AGP) and carrier, scleroglucan (SCLG) with improved antihypertensive activity. The SDAGP formulation was evaluated for physicochemical properties and in vitro/in vivo lung deposition. Further, antihypertensive activity was studied by monocrotaline (MCT) induced rat model. RESULTS: The SDAGP exhibited mean median aerodynamic diameter (MMAD) and fine particle fraction (FPF) of 3.37 ± 0.47 µm and 60.24 ± 0.98%. The in vivo absorption profile of final formulation reflected increased lung deposition of AGP at the end of 24 h with no signs of inflammation and toxicity. Moreover, SDAGP formulation confirmed enhanced antihypertensive activity. CONCLUSION: The results proved use of AGP and SCLG as a novel bioactive and carrier with enhanced lung deposition and pulmonary antihypertensive activity.
Asunto(s)
Antihipertensivos , Diterpenos , Portadores de Fármacos , Inhaladores de Polvo Seco , Glucanos , Administración por Inhalación , Animales , Antihipertensivos/administración & dosificación , Antihipertensivos/química , Antihipertensivos/farmacocinética , Antihipertensivos/toxicidad , Diterpenos/administración & dosificación , Diterpenos/química , Diterpenos/farmacocinética , Diterpenos/toxicidad , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Glucanos/administración & dosificación , Glucanos/química , Glucanos/farmacocinética , Glucanos/toxicidad , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/tratamiento farmacológico , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Monocrotalina , Tamaño de la Partícula , Ratas WistarRESUMEN
Background. Oxybenzone, a broad spectrum sunscreen agent widely used in the form of lotion and cream, has been reported to cause skin irritation, dermatitis, and systemic absorption. Aim. The objective of the present study was to formulate oxybenzone loaded microsponge gel for enhanced sun protection factor with reduced toxicity. Material and Method. Microsponge for topical delivery of oxybenzone was successfully prepared by quasiemulsion solvent diffusion method. The effects of ethyl cellulose and dichloromethane were optimized by the 3(2) factorial design. The optimized microsponges were dispersed into the hydrogel and further evaluated. Results. The microsponges were spherical with pore size in the range of 0.10-0.22 µm. The optimized formulation possesses the particle size and entrapment efficiency of 72 ± 0.77 µm and 96.9 ± 0.52%, respectively. The microsponge gel showed the controlled release and was nonirritant to the rat skin. In creep recovery test it had shown highest recovery indicating elasticity. The controlled release of oxybenzone from microsponge and barrier effect of gel result in prolonged retention of oxybenzone with reduced permeation activity. Conclusion. Evaluation study revealed remarkable and enhanced topical retention of oxybenzone for prolonged period of time. It also showed the enhanced sun protection factor compared to the marketed preparation with reduced irritation and toxicity.
RESUMEN
The progress in the development of DPI technology has boosted the use of sensitive drug molecules for lung diseases. However, delivery of these molecules from conventional DPI to the active site still poses a challenge with respect to deposition efficiency in the lung. At same time, serious systemic side effects of drugs have become a cause for concern. The developed budesonide loaded biopolymer based controlled release DPI had shown maximum in vitro lung deposition with least toxicity. The subject of present study, lactose-free budesonide loaded biopolymer based DPI, further corroborates the great potential of antiasthmatic drugs. This technology is expected to revolutionize the approaches towards enhanced therapeutic delivery of prospective drugs.